Spermidine as an epigenetic regulator of autophagy in neurodegenerative disorders

European Journal of Pharmacology, Journal Year: 2024, Volume and Issue: 979, P. 176823 - 176823

Published: July 18, 2024

Autophagy is an abnormal protein degradation and recycling process that impaired in various neurological diseases like Alzheimer's disease (AD), Parkinson's (PD), Huntington's disease. Spermidine a natural polyamine found plant- meat-based diets can induce autophagy, decreased neurodegenerative diseases. It acts on epigenetic enzymes E1A-binding p300, HAT Iki3p Sas3p, α-tubulin acetyltransferase 1 modulate autophagy. Histone modifications acetylation, phosphorylation, methylation could influence epigenetically regulated disorders with many miRNAs. Polyamine regulation plays essential role the pathogenesis of AD PD. Therefore, this review, we discuss miRNAs involved autophagy spermidine as enhancer. The alterations spermidine-mediated Beclin-1, LC3-II, p62 genes other PD-associated impact these With ever-growing data such promising effects feel it be target area worth further detailed studies.

Language: Английский

---

The potential role of gut microbiota-derived metabolites as regulators of metabolic syndrome-associated mitochondrial and endolysosomal dysfunction in Alzheimer’s disease

Experimental & Molecular Medicine, Journal Year: 2024, Volume and Issue: 56(8), P. 1691 - 1702

Published: Aug. 1, 2024

Although the role of gut microbiota (GMB)-derived metabolites in mitochondrial and endolysosomal dysfunction Alzheimer's disease (AD) under metabolic syndrome remains unclear, deciphering these host-metabolite interactions represents a major public health challenge. Dysfunction mitochondria networks (ELNs) plays crucial can exacerbate AD progression, highlighting need to study their reciprocal regulation for better understanding how is linked syndrome. Concurrently, disorders are associated with alterations composition GMB. Recent evidence suggests that changes GMB its may be involved pathology. This review highlights mechanisms syndrome-mediated development, focusing on interconnected roles dysfunction, ELN abnormalities, metabolites. We also discuss pathophysiological GMB-derived metabolites, including amino acids, fatty other extracellular vesicles, mediating effects dysfunction. Finally, this proposes therapeutic strategies by directly modulating functions through targeting

Language: Английский

---

Role of microglia autophagy and mitophagy in age-related neurodegenerative diseases

Frontiers in Aging Neuroscience, Journal Year: 2023, Volume and Issue: 14

Published: April 26, 2023

Microglia, characterized by responding to damage, regulating the secretion of soluble inflammatory mediators, and engulfing specific segments in central nervous system (CNS), function as key immune cells CNS. Emerging evidence suggests that microglia coordinate responses CNS play a pivotal role pathogenesis age-related neurodegenerative diseases (NDDs). Remarkably, autophagy participates regulation subcellular substances, which includes degradation misfolded proteins other harmful constituents produced neurons. Therefore, regulates neuronal homeostasis maintenance process neuroinflammation. In this review, we aimed at highlighting NDDs. Besides mechanistic co-interaction between different kinds NDDs, also emphasized potential therapeutic agents approaches could be utilized onset progression these through modulating autophagy, including promising nanomedicines. Our review provides valuable reference for subsequent studies focusing on treatments disorders. The exploration development nanomedicines greatly enhances current understanding

Language: Английский

---

The Molecular Role of Polyamines in Age-Related Diseases: An Update

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(22), P. 16469 - 16469

Published: Nov. 17, 2023

Polyamines (Pas) are short molecules that exhibit two or three amine groups positively charged at a physiological pH. These small present in high concentrations wide variety of organisms and tissues, suggesting they play an important role cellular physiology. include spermine, spermidine, putrescine, which roles age-related diseases have not been completely elucidated. Aging is natural process, defined as the time-related deterioration functions; it considered risk factor for degenerative such cardiovascular, neurodegenerative, musculoskeletal diseases; arthritis; even cancer. In this review, we provide new perspective on participation Pas molecular processes related to diseases, focusing our attention Alzheimerߣs disease, Parkinsonߣs osteoarthritis, sarcopenia, osteoporosis. This leads us propose function novel biomarkers with main purpose achieving alternatives healthier aging.

Language: Английский

---

Counteracting Immunosenescence—Which Therapeutic Strategies Are Promising?

Biomolecules, Journal Year: 2023, Volume and Issue: 13(7), P. 1085 - 1085

Published: July 6, 2023

Aging attenuates the overall responsiveness of immune system to eradicate pathogens. The increased production pro-inflammatory cytokines by innate cells under basal conditions, termed inflammaging, contributes impaired towards pathogen-mediated stimulation and limits antigen-presenting activity. Adaptive responses are attenuated as well due lowered numbers naïve lymphocytes their antigen-specific stimulation. Additionally, immunoregulatory cell types, comprising regulatory T myeloid-derived suppressor cells, that inhibit activity adaptive elevated. This review aims summarize our knowledge on cellular molecular causes immunosenescence while also taking into account senescence effects constitute evasion mechanisms in case chronic viral infections cancer. For tumor therapy numerous nanoformulated drugs have been developed overcome poor solubility compounds enable cell-directed delivery order restore functions, e.g., addressing dysregulated signaling pathways. Further, nanovaccines which efficiently address mount sustained anti-tumor clinically evaluated. senolytics selectively deplete senescent being tested a number clinical trials. Here we discuss potential use such improve anti-aging therapy.

Language: Английский

---